title: Lefty A protein inhibits TGF-β1-mediated apoptosis in human renal tubular epithelial cells.
abstract: This study aimed to examine the effects of Lefty A protein on transforming growth factor-β1 (TGF-β1)-mediated apoptosis in human renal tubular epithelial cells (HK-2). HK-2 cells were transfected with the human Lefty gene to induce the secretion of endogenous Lefty A protein. Following exposure of the HK-2 cells to recombinant human TGF-β1 (10 ng/ml), p-Smad2/3 protein levels were examined by western blot analysis, and cellular apoptosis was detected by flow cytometry 6, 12, 24 and 48 h following TGF-β1 treatment. Coculture of renal tubular epithelial cells with TGF-β1 resulted in a significant increase in p-Smad2/3 protein levels and the rate of cell apoptosis, which were attenuated by liposome-mediated transfection with the Lefty gene. Lefty A protein was able to inhibit the TGF-β1/Smad signaling pathway and markedly attenuate TGF-β1-mediated apoptosis in human renal tubular epithelial cells. Taken together, these results indicated that the TGF-β1/Smad signaling pathway most likely mediates apoptosis in renal tubular epithelial cells. In addition, Lefty A protein is capable of inhibiting the TGF-β1/Smad pathway to reduce TGF-β1/Smad-mediated apoptosis in renal tubular epithelial cells. This study may provide novel insights into the prevention and treatment of urinary tract obstruction disease using Lefty A protein.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China.
authors.forename: Ren-Ping
authors.initials: RP
authors.lastname: Zheng
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Zhou
authors.forename: Chang-Gen
authors.initials: CG
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D055458:Left-Right Determination Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D024101:Mitochondrial Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D024101:Mitochondrial Proteins; D053773:Transforming Growth Factor beta1